Nymalize

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Hypotension

Blood pressure should be carefully monitored during
treatment with NYMALIZE. In clinical studies of patients with subarachnoid hemorrhage, about 5% of nimodipine-treated patients compared to 1% of
placebo-treated patients had hypotension and about 1% of nimodipine-treated
patients left the study because of this. [see ADVERSE REACTIONS].

Possible Increased Risk of Adverse Reactions in Patients
with Cirrhosis

Given that the plasma levels of nimodipine are increased
in patients with cirrhosis, these patients are at higher risk of adverse
reactions. Therefore, monitor blood pressure and pulse rate closely and
administer a lower dosage [see DOSAGE AND ADMINISTRATION, CLINICAL
PHARMACOLOGY].

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

In a two-year study in rat, the incidences of
adenocarcinoma of the uterus and Leydig cell adenoma of the testes were
increased at 1800 ppm nimodipine in the diet (approximately 90-120 mg/kg/day).
The increases were not statistically significant, however, and the higher rates
were within the historical control range for these tumors. Nimodipine was found
not to be carcinogenic in a 91-week mouse study, but the high dose of 1800 ppm
nimodipine in the diet (approximately 550-775 mg/kg/day) was associated with an
increased mortality rate.

Mutagenicity studies, including the Ames, micronucleus,
and dominant lethal assays, were negative.

Impairment of Fertility

Nimodipine did not impair the fertility and general
reproductive performance of male and female rats following oral doses of up to
30 mg/kg/day when administered prior to mating and continuing in females to day
7 of pregnancy. This dose in a rat is similar to a clinical dose of 60 mg every
4 hours in a 60 kg patient, on a body surface area (mg/m²) basis.

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are no adequate and well controlled studies in
pregnant women to directly assess the effect on human fetuses. NYMALIZE should
be used during pregnancy only if the potential benefit justifies the potential
risk to the fetus.

Nimodipine has been shown to have a teratogenic effect in
two studies in rabbit. In one study, incidences of malformations and stunted
fetuses were increased at oral doses of 1 mg/kg/day and 10 mg/kg/day
administered throughout organogenesis but not at 3 mg/kg/day. In the second
study, an increased incidence of stunted fetuses was seen at 1 mg/kg/day but
not at higher doses (3 mg/kg/day and 10 mg/kg/day). Nimodipine was embryotoxic,
causing resorption and stunted growth of fetuses in rats at 100 mg/kg/day
administered orally throughout organogenesis. In two other rat studies, doses
of 30 mg/kg/day nimodipine administered orally throughout organogenesis and
continued until sacrifice (day 20 of pregnancy or day 21 postpartum) were
associated with higher incidences of skeletal variation, stunted fetuses, and
stillbirths but no malformations.

Nursing Mothers

Nimodipine and/or its metabolites have been detected in
rat milk at concentrations much higher than in maternal plasma. It is not known
whether the drug is excreted in human milk. Because many drugs are excreted in
human milk and because of the potential for serious adverse reactions in
nursing infants from NYMALIZE, a decision should be made whether to discontinue
nursing or discontinue the drug, taking into account the importance of the drug
to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not
been established.

Geriatric Use

Clinical studies of nimodipine did not include sufficient
numbers of subjects aged 65 and over to determine whether they had a different
clinical response than younger subjects. Other reported clinical experience has
not identified differences in responses between the elderly and younger
patients. In general, dosing in elderly patients should be cautious, reflecting
the greater frequency of decreased hepatic, renal or cardiac function, and of
concomitant disease or other drug therapy [see CLINICAL PHARMACOLOGY].

Last reviewed on RxList: 5/23/2013
This monograph has been modified to include the generic and brand name in many instances.